title: Diaphragm muscle atrophy in the mouse after long-term mechanical ventilation.
abstract: BACKGROUND
  Mechanical ventilation (MV) is a life-saving measure, but full ventilator support causes ventilator-induced diaphragm atrophy (VIDA). Previous studies of VIDA have relied on human biopsies or a rat model. If MV can induce diaphragm atrophy in mice, then mechanistic study of VIDA could be explored via genetic manipulation.
  
  
  RESULTS
  We show that 18 hours of MV in mice results in a 15% loss of diaphragm weight and a 17% reduction in fiber cross-sectional area. Important catabolic cascades are activated in this mouse model: transcription of the ubiquitin ligases, atrogin and MuRF1, and the apoptotic marker, Bim, are increased; the marker of autophagy, LC3, is induced at the protein level and shows a punctate distribution in diaphragm muscle fibers.
  
  
  CONCLUSIONS
  This mouse model recapitulates the key pathophysiological findings of other models of VIDA, and it will enable the genetic manipulation required to fully explore the mechanisms underlying this important process.
authors.affiliation: Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, VA Palo Alto Health Care System, 300 Pasteur Drive, Stanford, California 94305-5407, USA.
authors.forename: Huibin
authors.initials: H
authors.lastname: Tang
authors.forename: Myung
authors.initials: M
authors.lastname: Lee
authors.forename: Amanda
authors.initials: A
authors.lastname: Khuong
authors.forename: Erika
authors.initials: E
authors.lastname: Wright
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Shrager
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001784:Blood Gas Analysis; D001835:Body Weight / Q000502:physiology; D003964:Diaphragm / Q000503:physiopathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008868:Microtubule Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: C120761:LC-3 protein, Ovis aries; D008868:Microtubule Proteins; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; D018995:Myosin Heavy Chains
keywords: autophagy; diaphragm; mechanical ventilation; mouse; muscle atrophy